Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication MAVYRET is indicated for the treatment of adult and pediatric patients 3 years and older with acute or chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5 or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A). FDA label
Also known as MAVYRET®
Glecaprevir/Pibrentasvir Adult Formulation · 13 trials · 8 indications
Number of non-cirrhotic treatment-experienced HCV genotype 1 with a NS5Ai inhibitor + SOF +/-RBV participants with undetectable HCV RNA (HCV RNA \<Lower Limit of Quantification -LLOQ) 12 weeks after completing G/P 300 mg/100 mg daily for 12 weeks (Arm A) vs. 16 weeks of G/P 300 mg/100 mg daily (Arm B)
Number of cirrhotic participants who are treatment experienced with a NS5A inhibitor + SOF +/RBV with undetectable HCV RNA 12 weeks after completing G/P plus RBV for 12 wks vs. G/P for 16 Wks
Number of subjects who discontinued G/P due to adverse events
SVR12 is defined as the hepatitis C virus (HCV) ribonucleic acid (RNA) level less than the lower limit of quantification (\< LLOQ) 12 weeks after the last dose of study treatment. Efficacy was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants achieving SVR12 was greater than 90.5%.
SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (LLOQ; less than 15 IU/mL) 12 weeks after the last dose of study drug.
Sustained virologic response 12 weeks post-treatment (SVR12) was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (LLOQ; less than 15 IU/mL) 12 weeks after the last dose of study drug.
SVR12 was defined as plasma HCV RNA level less than 15 IU/mL 12 weeks after the last dose of study drug.
SVR12 was defined as plasma HCV RNA level less than 15 IU/mL 12 weeks after the last actual dose of study drug.
SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (LLOQ; 15 IU/mL) 12 weeks after the last dose of study drug. The 95% confidence interval (95%CI) was calculated using the Wilson's score method. Efficacy was to be established if the lower bound of the 95%CI was greater than the threshold of 92.4%, based on the historical rate observed in glecaprevir/pibrentasvir registrational studies in treatment-naïve, non-cirrhotic patients (98.4%) minus a margin of 6%.
SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (\<LLOQ; less than 15 IU/mL) 12 weeks after the last dose of study drug. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% confidence interval (CI) for the percentage of participants with HCV GT1, GT2, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 94% in the PP population. Efficacy analyses were performed following a fixed-sequence testing procedure to control the type I error rate. The percentage of participants achieving SVR12 was summarized with a 2-sided 95% CI, calculated using the normal approximation to the binomial distribution. If the number of participants who failed to achieve SVR12 rate was less than 5, the Wilson's score method was used to calculate the CI.
SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants with HCV GT1, GT2, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 93% in the ITT population. Primary efficacy analyses were performed following a fixed-sequence testing procedure to control the type I error rate. The percentage of participants achieving SVR12 was summarized with a 2-sided 95% CI, calculated using the normal approximation to the binomial distribution. If the number of participants who failed to achieve SVR12 rate was less than 5, the Wilson's score method was used to calculate the CI.
SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.
SVR12 is defined as hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (LLOQ; less than 15 IU/mL) 12 weeks after the last actual dose of study drug.
SVR12 defined as unquantifiable HCV RNA (less than the lower limit of quantification \[LLOQ\], target detected \[TD\] or target not detected \[TND\]) at study visit 12 weeks post treatment (Week 16). If a participant did not have HCV RNA measurement at Week 16, the participant was considered as SVR12 failure, unless there were preceding and subsequent HCV RNA measurements that were both LLOQ (either TD or TND).
Study protocol required reporting of (1) AEs Grade greater than or equal to 2, (2) AEs that led to a change in study treatment regardless of grade and (3) AEs meeting ICH definition of serious AE (SAE) or Expedited AE (EAE) reporting requirement. DAIDS AE Grading Table (V2.1) and DAIDS EAE Manual (V2.0) were used.
Number of participants who completed 4 weeks of treatment without discontinuation due to AEs
The area under the plasma concentration-time curve (AUC) is a method of measurement of the total exposure of a drug in blood plasma. The steady-state exposure of GLE was measured up to 24 hours after dosing at Week 2 and estimated using non-compartmental analysis.
The area under the plasma concentration-time curve (AUC) is a method of measurement of the total exposure of a drug in blood plasma. The steady-state exposure of PIB was measured up to 24 hours after dosing at Week 2 and estimated using non-compartmental analysis.
| Arm | Type | Description |
|---|---|---|
| Arm A: G/P 300 mg/120 mg QD for 12 Wks | EXPERIMENTAL | Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg (3 Glecaprevir/Pibrentasvir (G/P) 100mg/40mg Tablets once-daily by mouth) for 12 weeks. |
| Arm B: G/P 300 mg/120 mg QD for 16 Wks | EXPERIMENTAL | Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once-daily by mouth for 16 weeks (G/P 300 mg/120 mg QD for 16 Wks) |
| Arm C: G/P 300 mg/120 mg QD + RBV 12 Wks | EXPERIMENTAL | Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily plus Ribavirin 200Mg Tablet (2-3 tablets) twice a day for 12 weeks (G/P 300 mg/120 mg QD + RBV 12 Wks) |
| Arm D: G/P 300 mg/120 mg QD for 16 Wks | EXPERIMENTAL | Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily for 16 weeks (G/P 300 mg/120mg QD for 16 Wks) |
| Glecaprevir/Pibrentasvir | EXPERIMENTAL | Participants treated once daily (QD) with glecaprevir/pibrentasvir 300 mg/120 mg for 8 weeks. |
| Arm A: Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 weeks | EXPERIMENTAL | Arm A: Hepatitis C virus (HCV) genotype (GT) 1 to GT6 participants without cirrhosis (fibrosis stage F2 to F3) received glecaprevir (GLE)/pibrentasvir (PIB) 300 mg/120 mg once daily (QD) for 8 weeks. |
| Arm B: GLE/PIB for 12 Weeks | EXPERIMENTAL | Arm B: HCV GT1 to GT6 participants with compensated cirrhosis (F4) received GLE/PIB 300 mg/120 mg QD for 12 weeks. |
| Placebo / Glecaprevir/Pibrentasvir | EXPERIMENTAL | Participants received placebo to glecaprevir/pibrentasvir for 8 or 16 weeks during the DB treatment period followed by glecaprevir/pibrentasvir (300 mg/120 mg) once daily for 8 or 16 weeks during the open-label (OL) treatment period. In each period participants received treatment for 8 weeks with the exception of treatment-experienced, genotype 3-infected participants who received treatment for 16 weeks. |
| Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 weeks | EXPERIMENTAL | Glecaprevir (GLE)/Pibrentasvir (PIB) 300 mg/120 mg once daily (QD) for 8 weeks. |
| GLE/PIB for 8 weeks | EXPERIMENTAL | HCV genotype 1,2,4-6 non-cirrhotic, treatment-naive or treatment-experienced; genotype 3 non-cirrhotic, treatment-naïve participants treated with glecaprevir/pibrentasvir (GLE/PIB): three 100 mg/40 mg co-formulated tablets once daily with food for 8 weeks |
| GLE/PIB for 12 weeks | EXPERIMENTAL | HCV genotype 1,2,4-6 compensated cirrhosis, treatment-naive or treatment-experienced; genotype 3 compensated cirrhosis, treatment- naïve participants treated with glecaprevir/pibrentasvir (GLE/PIB): three 100 mg/40 mg co-formulated tablets once daily with food for 12 weeks |
| GLE/PIB for 16 weeks | EXPERIMENTAL | HCV genotype 3 non-cirrhotic or with compensated cirrhosis, treatment-experienced participants treated with glecaprevir/pibrentasvir (GLE/PIB): three 100 mg/40 mg co-formulated tablets once daily with food for 16 weeks |
| Glecaprevir/Pibrentasvir for 8 Weeks | EXPERIMENTAL | Non-cirrhotic participants with hepatitis C virus genotype 5 or 6 received oral glecaprevir/pibrentasir (300 mg/120 mg) once daily with food for 8 weeks, according to label. |
| Glecaprevir/Pibrentasvir for 12 Weeks | EXPERIMENTAL | Participants with hepatitis C virus genotype 5 or 6 and compensated cirrhosis received oral glecaprevir/pibrentasir (300 mg/120 mg) once daily with food for 12 weeks, according to label. |
| Glecaprevir/Pibrentasvir + SOF + RBV for 12 weeks | EXPERIMENTAL | Participants without cirrhosis who had non-genotype 3 infection and were naïve to protease inhibitor (PI) and/or nonstructural viral protein 5A inhibitor (NS5Ai) prior to participation in AbbVie HCV parent study received daily treatment with glecaprevir/pibrentasvir (GLE/PIB) 300 mg/120 mg plus sofosbuvir (SOF) 400 mg plus twice-daily weight-based ribavirin (RBV) 600 mg - 1200 mg daily total for 12 weeks. |
| Glecaprevir/Pibrentasvir + SOF + RBV for 16 weeks | EXPERIMENTAL | Participants with genotype 3, and/or compensated cirrhosis, and/or experience with PI and/or NS5Ai prior to participation in Abbvie HCV parent study received daily treatment with GLE/PIB 300 mg/120 mg plus SOF 400 mg plus twice-daily weight-based RBV 600 mg - 1200 mg daily total for 16 weeks. |
| Glecaprevir/Pibrentasvir (G/P) | EXPERIMENTAL | Participants were assigned to receive G/P FDC tablets to be taken orally once daily for 4 weeks (Step 1). Participants who experienced HCV re-infection, suspected relapse, virologic failure, or undefined post-treatment viremia in Step 1 were offered to enter Step 2 for re-treatment. HCV re-treatment regimens may have included G/P FDC tablets orally once daily for 8-16 weeks, or alternate regimens through clinical care. |
| Cohort 1: Adult Formulation; 12 to < 18 years | EXPERIMENTAL | Adolescents aged 12 to \< 18 years old received the adult formulation of glecaprevir (GLE)/pibrentasvir (PIB) 100 mg/ 40 mg co-formulated film-coated tablets for a once daily (QD) total dose of 300 mg/120 mg by mouth for 8, 12, or 16 weeks depending on HCV genotype, cirrhosis status, and prior treatment experience. |
| Cohort 2: Pediatric Formulation; 9 to < 12 years | EXPERIMENTAL | Children aged 9 to \< 12 years old received a pediatric formulation of GLE + PIB as small film-coated granules taken with a small amount of food once daily for 8, 12, or 16 weeks depending on HCV genotype, cirrhosis status, and prior treatment experience. The initial proposed dose for children 9 to \< 12 years old (30 to \< 45 kg) was GLE 200 mg + PIB 75 mg. After PK analysis from the first 6 enrolled participants the dose was adjusted to GLE 250 mg + PIB 100 mg. |
| Cohort 3: Pediatric Formulation; 6 to < 9 years | EXPERIMENTAL | Children aged 6 to \< 9 years old received a pediatric formulation of GLE + PIB as small film-coated granules taken with a small amount of food once daily for 8, 12, or 16 weeks depending on HCV genotype, cirrhosis status, and prior treatment experience. The initial proposed dose for children 6 to \< 9 years old (20 to \< 30 kg) was GLE 160 mg + PIB 60 mg. After PK analysis from the first 6 enrolled participants the dose was adjusted to GLE 200 mg + PIB 80 mg. |
| Cohort 4: Pediatric Formulation; 3 to < 6 years | EXPERIMENTAL | Children aged 3 to \< 6 years old received a pediatric formulation of GLE + PIB as small film-coated granules taken with a small amount of food once daily for 8, 12, or 16 weeks depending on HCV genotype, cirrhosis status, and prior treatment experience. The initial proposed dose for children 3 to \< 6 years old (12 to \< 20 kg) was GLE 120 mg + PIB 45 mg. After PK analysis from the first 5 enrolled participants the dose was adjusted to GLE 150 mg + PIB 60 mg. |
| Name | Type | Description |
|---|---|---|
| Glecaprevir/Pibrentasvir (G/P) 300mg/120mg | DRUG | daily |
| Ribavirin 200Mg Tablet | DRUG | Weight-based 1000-1200 mg |
| Glecaprevir/Pibrentasvir (GLE/PIB) | DRUG | Oral tablets |
| Glecaprevir/Pibrentasvir | DRUG | Film-coated tablet |
| Placebo | DRUG | Matching placebo tablet for oral administration |
| Sofosbuvir | DRUG | Tablet for oral administration |
| Ribavirin | DRUG | Tablet for oral administration |
| Glecaprevir/Pibrentasvir (G/P) | DRUG | Fixed-dose combination (FDC) tablets containing 100 mg of glecaprevir and 40 mg of pibrentasvir; administered as 3 tablets orally. |
| Glecaprevir/Pibrentasvir Adult Formulation | DRUG | Co-formulated film-coated tablet (100 mg/40 mg) |
| Glecaprevir + Pibrentasvir Pediatric Formulation | DRUG | Film-coated pellets/granules (15.67%/8.25%) administered by mixing with a small amount (1-2 teaspoons) of a soft food vehicle, such as hazelnut spread, Greek yogurt, or peanut butter. |
Inclusion Criteria: 1. Male or female at least 18 years of age at time of screening. 2. A history of previous treatment with an NS5A-inhibitor plus sofosbuvir therapy ± RBV for chronic HCV genotype 1 infection. 3. Treatment must have been completed at least 1 month prior to Screening Visit. 4. Scre...
Glecaprevir/pibrentasvir is used to treat chronic hepatitis C virus (HCV) infection, including genotypes 1 through 6, in adults and adolescents. It is also being studied in acute HCV infection and in patients with compensated cirrhosis or HIV co-infection. It is a small molecule antiviral therapy in the infectious disease therapeutic area.
Glecaprevir/pibrentasvir is developed and manufactured by AbbVie Inc., which trades on the New York Stock Exchange under the ticker ABBV. AbbVie is the sponsor of the clinical trial program evaluating the fixed-dose combination in hepatitis C virus infection.
Glecaprevir/pibrentasvir has been evaluated in Phase 3 clinical development, with nine completed trials in the program. The studies include both Phase 2 and Phase 3 trials, and all nine have been completed, with no active trials currently listed.
Completed trials include NCT04903626, a Phase 3 study in adults and adolescents with acute HCV infection enrolling 286 participants, and NCT03222583, a Phase 3 study in non-cirrhotic Asian adults with chronic HCV genotypes 1 to 6 enrolling 546 participants. Other completed studies include NCT04042740 and NCT03235349.
Across the nine completed clinical trials, a total of 1,979 participants have been enrolled. The trials were conducted in multiple countries including the United States, Australia, Austria, Canada, France, Germany, Italy, Spain, China, South Korea, Singapore, and Brazil.